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1.
Clin Transl Radiat Oncol ; 45: 100730, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38317679

ABSTRACT

Purpose/objectives: The growing use of stereotactic body radiotherapy (SBRT) in metastatic cancer has led to its use in varying anatomic locations. The objective of this study was to review our institutional SBRT experience for axillary metastases (AM), focusing on outcomes and process. Materials/methods: Patients treated with SBRT to AM from 2014 to 2022 were reviewed. Cumulative incidence functions were used to estimate the incidence of local failure (LF), with death as competing risk. Kaplan-Meier method was used to estimate progression-free (PFS) and overall survival (OS). Univariate regression analysis examined predictors of LF. Results: We analyzed 37 patients with 39 AM who received SBRT. Patients were predominantly female (60 %) and elderly (median age: 72). Median follow-up was 14.6 months. Common primary cancers included breast (43 %), skin (19 %), and lung (14 %). Treatment indication included oligoprogression (46 %), oligometastases (35 %) and symptomatic progression (19 %). A minority had prior overlapping radiation (18 %) or surgery (11 %). Most had prior systemic therapy (70 %).Significant heterogeneity in planning technique was identified; a minority of patient received 4-D CT scans (46 %), MR-simulation (21 %), or contrast (10 %). Median dose was 40 Gy (interquartile range (IQR): 35-40) in 5 fractions, (BED10 = 72 Gy). Seventeen cases (44 %) utilized a low-dose elective volume to cover remaining axilla.At first assessment, 87 % had partial or complete response, with a single progression. Of symptomatic patients (n = 14), 57 % had complete resolution and 21 % had improvement. One and 2-year LF rate were 16 % and 20 %, respectively. Univariable analysis showed increasing BED reduced risk of LF. Median OS was 21.0 months (95 % [Confidence Interval (CI)] 17.3-not reached) and median PFS was 7.0 months (95 % [CI] 4.3-11.3). Two grade 3 events were identified, and no grade 4/5. Conclusion: Using SBRT for AM demonstrated low rates of toxicity and LF, and respectable symptom improvement. Variation in treatment delivery has prompted development of an institutional protocol to standardize technique and increase efficiency. Limited followup may limit detection of local failure and late toxicity.

2.
Radiother Oncol ; 191: 110077, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38176656

ABSTRACT

This exploratory study is a follow up to our previous investigation of immune response in the circulation of high-grade Gleason 9 prostate cancer patients treated with EBRT + BT compared to EBRT alone. Notably, EBRT + BT demonstrates the potential to elicit an effect on CD4/CD8 ratio which may have attributed to improved clinical response to therapy. Our findings show promise for leveraging circulating immune cells as predictive biomarkers for radiotherapy response.


Subject(s)
Brachytherapy , Prostatic Neoplasms , Male , Humans , Brachytherapy/adverse effects , Prostatic Neoplasms/radiotherapy , Retrospective Studies , Prostate-Specific Antigen , CD8-Positive T-Lymphocytes , Radiotherapy Dosage
3.
Clin Oncol (R Coll Radiol) ; 35(1): 20-28, 2023 01.
Article in English | MEDLINE | ID: mdl-35948465

ABSTRACT

AIMS: To evaluate oncological and renal function outcomes of stereotactic body radiotherapy (SBRT) for medically inoperable patients with localised renal cell carcinoma. MATERIALS AND METHODS: Consecutive patients treated with curative intent SBRT (30-45 Gy in five fractions or 42 Gy in three fractions) were included. Data on local control (Response Evaluation Criteria in Solid Tumors [RECIST] v1.1), distant metastasis, impact on estimated glomerular filtration rate (eGFR) and proportional ipsilateral and contralateral renal functions (measured through renal scans) were collected. Univariate and multivariable analyses were conducted to determine association of variables with oncological and renal function outcomes. RESULTS: Seventy-four patients were analysed. The median follow-up was 27.8 months (interquartile range 17.6-41.7). Fifty-seven per cent had tumours ≥ T1b. One-, 2- and 4-year cumulative incidence of local failure was 5.85, 7.77 and 7.77%, respectively. The cumulative incidence of distant metastasis at 2 years was 4.24%. On multivariable analysis, a lower planning target volume (PTV) mean dose (P = 0.019) and a larger PTV (P = 0.005) were significantly associated with the risk of developing local failure. A lower PTV maximum dose (P = 0.039) was significantly associated with the risk of developing distant metastasis. The median change in global eGFR (ml/min) from pre-SBRT levels was -7.0 (interquartile range -14.5 to -1.0) at 1 year and -11.5 (interquartile range -19.5 to -4.0) at 2 years. The proportion of ipsilateral (differential) renal function decreased over time from 47% of overall renal function pre-SBRT to 36% at 2 years, whereas the proportion of contralateral renal function correspondingly improved. On multivariable analysis, a higher volume of uninvolved renal cortex (P < 0.0001) was significantly associated with a smaller decrease in eGFR over time. CONCLUSION: In this large institutional cohort, oncological outcomes of renal cell carcinoma treated with SBRT were favourable and a longitudinal decline in renal function in the ipsilateral kidney and compensatory increase in the contralateral kidney were observed. Clinical and dosimetric factors were significantly associated with oncological and renal function outcomes.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Lung Neoplasms , Radiosurgery , Humans , Carcinoma, Renal Cell/radiotherapy , Radiosurgery/adverse effects , Kidney Neoplasms/radiotherapy , Kidney Neoplasms/pathology , Kidney/physiology , Kidney/pathology , Retrospective Studies , Lung Neoplasms/pathology
4.
Clin Oncol (R Coll Radiol) ; 33(7): 468-475, 2021 07.
Article in English | MEDLINE | ID: mdl-33775496

ABSTRACT

AIMS: We report on the first prospective series of patient-reported quality of life (QoL) following stereotactic body radiation therapy (SBRT) for primary kidney cancer. MATERIALS AND METHODS: Patients were treated on a multi-institutional prospective cohort study with 30-42 Gy SBRT in three or five fractions. QoL assessments were carried out using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-15 Palliative (EORTC-QLQ-C15-PAL), the Functional Assessment of Cancer Therapy-Kidney Symptom Index-19 (FACT FKSI-19) and the EuroQol-5D-3L tools at baseline, 1 week, and 1, 3 and 6 months post-treatment. QoL over time was analysed using linear mixed modelling, pairwise and anchor-based analyses. RESULTS: Twenty-eight patients were included. No significant reduction in any QoL metric was observed on repeated measures. However, a trend to reduced EORTC global QoL and fatigue was observed at 1 week, with improvement over time in other symptom scores such as pain, appetite and nausea. On pairwise analysis, there were statistically significant reductions in global QoL at 1 week (with subsequent recovery) and dyspnoea at 6 months post-SBRT. Trends to improved pain, appetite and nausea were observed following SBRT. Less than half of patients reported stable or better EORTC global QoL at 1 week. For all other QoL and symptom scales, most patients had reported stable or better scores at all times, with a slight proportional improvement in emotional functioning, nausea, fatigue, pain and appetite, and a slight worsening of physical functioning and dyspnoea over time. CONCLUSIONS: SBRT results in well-preserved QoL in the weeks to months following treatment for primary kidney cancer.


Subject(s)
Kidney Neoplasms , Radiosurgery , Humans , Kidney Neoplasms/radiotherapy , Kidney Neoplasms/surgery , Patient Reported Outcome Measures , Prospective Studies , Quality of Life , Radiosurgery/adverse effects , Surveys and Questionnaires
5.
Radiother Oncol ; 155: 80-85, 2021 02.
Article in English | MEDLINE | ID: mdl-33172830

ABSTRACT

This exploratory study evaluates immunological changes in high-risk Gleason 9 prostate cancer patients treated with EBRT+BT compared to EBRT alone. Notably, BT demonstrates the potential to elicit a T cell response which may support further investigation using circulating immune cells as predictive and prognostic biomarkers for radiotherapy response.


Subject(s)
Brachytherapy , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/radiotherapy , Radiotherapy Dosage , Retrospective Studies
6.
Clin Oncol (R Coll Radiol) ; 32(10): 647-655, 2020 10.
Article in English | MEDLINE | ID: mdl-32540281

ABSTRACT

AIMS: Higher mean lung dose (MLD) in breast cancer patients has been associated with pneumonitis, pulmonary fibrosis and secondary lung cancer primaries. This study examined MLD in a single institution from 2014 to 18 to assess trends in median MLD (Gy) over time and factors associated with higher MLD to determine best practices for limiting lung toxicity. MATERIALS AND METHODS: General linear regressions were analysed to determine significant change in median MLD over time in patients receiving conventional or hypofractionated schedules for whole breast/chest wall (WB) radiotherapy with or without sequential boost or simultaneous integrated boost, WB tangential radiotherapy only and WB locoregional radiotherapy. Univariate and multivariable linear regression analysed identified factors associated with MLD. RESULTS: In total, 3894 patients were included in the analysis. The total median MLD across all years was 6.8 Gy in patients treated with conventional fractionation and 3.4 Gy in patients treated with hypofractionation. A significant increase in MLD was observed between 2014 and 2018 in patients receiving conventional or hypofractionation, conventional WB treatment with locoregional radiotherapy, conventional WB radiotherapy with simultaneous integrated boost and hypofractionated WB radiotherapy with sequential boost. Increased MLD was significantly correlated with lower lung volume and larger treatment volume due to locoregional radiotherapy, inclusion of a boost, chest wall treatment and reverse decubitus or supine positioning (P < 0.0001). CONCLUSION: A significant increase in MLD was observed over the years in patients receiving conventional and hypofractionated radiotherapy. Techniques such as prone positioning should be considered to lower MLD, particularly for patients with predisposing pulmonary risk.


Subject(s)
Breast Neoplasms/radiotherapy , Lung/radiation effects , Organs at Risk/radiation effects , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Adjuvant/methods , Adult , Aged , Aged, 80 and over , Dose Fractionation, Radiation , Female , Humans , Middle Aged , Time Factors , Young Adult
7.
Radiother Oncol ; 141: 149-155, 2019 12.
Article in English | MEDLINE | ID: mdl-31522882

ABSTRACT

PURPOSE/OBJECTIVE: To report biochemical control associated with single fraction 15 Gy high-dose-rate brachytherapy (HDR-BT) boost followed by external beam radiation (EBRT) in patients with intermediate-risk prostate cancer. MATERIALS AND METHODS: A retrospective chart review of all patients with intermediate-risk disease treated with a real-time ultrasound-based 15 Gy HDR-BT boost followed by EBRT between 2009 and 2016 at a single quaternary cancer center was performed. Freedom from biochemical failure (FFBF), cumulative incidence of androgen deprivation therapy use for biochemical or clinical failure post-treatment (CI of ADT) and metastasis-free survival (MFS) outcomes were measured. RESULTS: 518 patients met the inclusion criteria for this study. Median age at HDR-BT was 67 years (IQR 61-72). 506 (98%) had complete pathologic information available. Of these, 146 (28%) had favorable (FIR) and 360 (69%) had unfavorable (UIR) intermediate-risk disease. 83 (16%) received short course hormones with EBRT + HDR. Median overall follow-up was 5.2 years. FFBF was 91 (88-94)% at 5 years. Five-year FFBF was 94 (89-99)% and 89 (85-94)% in FIR and UIR patients, respectively (p = 0.045). CI of ADT was 4 (2-6)% at 5 years. Five-year CI of ADT was 1 (0-3)% and 5 (2-8)% in FIR and UIR patients, respectively (p = 0.085). MFS was 97 (95-98)% at 5 years. Five-year MFS was 100 (N/A-100)% and 95 (92-98)% in FIR and UIR patients, respectively (p = 0.020). CONCLUSION: In this large cohort of intermediate-risk prostate cancer patients, 15 Gy HDR-BT boost plus EBRT results in durable biochemical control and low rates of ADT use for biochemical failure.


Subject(s)
Brachytherapy/methods , Prostatic Neoplasms/radiotherapy , Aged , Androgen Antagonists/therapeutic use , Humans , Male , Middle Aged , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Radiotherapy Dosage , Retrospective Studies
9.
Clin Oncol (R Coll Radiol) ; 31(9): 621-629, 2019 09.
Article in English | MEDLINE | ID: mdl-31126725

ABSTRACT

AIMS: We conducted a pooled analysis of four prospective stereotactic body radiotherapy (SBRT) trials of low- and intermediate-risk prostate cancer to evaluate the incidence of prostate-specific antigen (PSA) bounce and its correlation with the time-dose-fraction schedule. The correlation between bounce with PSA response at 4 years (nadir PSA < 0.4 ng/ml) and biochemical failure-free survival (BFFS) was also explored. MATERIALS AND METHODS: The study included four treatment groups: 35 Gy/five fractions once per week (QW) (TG-1; n = 84); 40 Gy/five fractions QW (TG-2; n = 100); 40 Gy/five fractions every other day (TG-3; n = 73); and 26 Gy/two fractions QW (TG-4; n = 30). PSA bounce was defined as a rise in PSA by 0.2 ng/ml (nadir + 0.2) or 2 ng/ml (nadir + 2.0) above nadir followed by a decrease back to nadir. Patients with fewer than three follow-up PSA tests were excluded from the pooled analysis. RESULTS: In total, 287 patients were included, with a median follow-up of 5.0 years. The pooled 5-year cumulative incidence of bounce by nadir + 2.0 was 8%. The 2-year cumulative incidences of PSA bounce by nadir + 0.2 were 28.9, 21, 19.6 and 16.7% (P = 0.12) and by nadir + 2.0 were 7.2, 8, 2.7 and 6.7% (P = 0.32) for TG-1 to TG-4, respectively. Multivariable analysis revealed that for nadir + 2.0, pre-treatment PSA (odds ratio 0.49; 95% confidence interval 0.26-0.97) correlated with PSA bounce. Although PSA bounce by nadir + 0.2 (odds ratio 0.10; 95% confidence interval 0.04-0.24) and nadir + 2.0 (odds ratio 0.29; 95% confidence interval 0.09-0.93) was associated with a lower probability of PSA response at 4 years, there was no association between bounce by nadir + 0.2 (hazard ratio 0.36; 95% confidence interval 0.08-1.74) or nadir + 2 (hazard ratio 1.77; 95% confidence interval 0.28-11.07) with BFFS. CONCLUSION: The incidence of PSA bounce was independent of time-dose-fraction schedule for prostate SBRT. One in 13 patients experienced a bounce high enough to be misinterpreted as biochemical failure, and clinicians should avoid early salvage interventions in these patients. There was no association between PSA bounce and BFFS.


Subject(s)
Prostate-Specific Antigen/metabolism , Prostatic Neoplasms/radiotherapy , Radiosurgery/methods , Aged , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies
10.
J Transl Med ; 17(1): 173, 2019 05 23.
Article in English | MEDLINE | ID: mdl-31122242

ABSTRACT

BACKGROUND: Prostate cancer is an extremely heterogeneous disease. Despite being clinically similar, some tumours are more likely to recur after surgery compared to others. Distinguishing those that need adjuvant or salvage radiotherapy will improve patient outcomes. The goal of this study was to identify circulating microRNA that could independently predict prostate cancer patient risk stratification after radical prostatectomy. METHODS: Seventy-eight prostate cancer patients were recruited at the Odette Cancer Centre in Sunnybrook Health Sciences Centre. All patients had previously undergone radical prostatectomy. Blood samples were collected simultaneously for PSA testing and miRNA analysis using NanoString nCounter technology. Of the 78 samples, 75 had acceptable miRNA quantity and quality. Patients were stratified into high- and low-risk categories based on Gleason score, pathological T stage, surgical margin status, and diagnostic PSA: patients with Gleason ≥ 8; pT3a and positive margin; pT3b and any margin; or diagnostic PSA > 20 µg/mL were classified as high-risk (n = 44) and all other patients were classified as low-risk (n = 31). RESULTS: Using our patient dataset, we identified a four-miRNA signature (miR-17, miR-20a, miR-20b, miR-106a) that can distinguish high- and low-risk patients, in addition to their pathological tumour stage. High expression of these miRNAs is associated with shorter time to biochemical recurrence in the TCGA dataset. These miRNAs confer an aggressive phenotype upon overexpression in vitro. CONCLUSIONS: This proof-of-principle report highlights the potential of circulating miRNAs to independently predict risk stratification of prostate cancer patients after radical prostatectomy.


Subject(s)
Biomarkers, Tumor/blood , Circulating MicroRNA/blood , Prostatectomy , Prostatic Neoplasms/blood , Prostatic Neoplasms/surgery , Aged , Cell Line, Tumor , Circulating MicroRNA/genetics , Humans , Male , Middle Aged , Prostatic Neoplasms/genetics
11.
Radiother Oncol ; 135: 170-177, 2019 06.
Article in English | MEDLINE | ID: mdl-31015164

ABSTRACT

BACKGROUND AND PURPOSE: To identify if, in intermediate risk prostate cancer (IR-PCa), the absolute percentage of biopsied tissue positive for pattern 4 disease (APP4) may be a predictor of outcome. MATERIALS AND METHODS: 411 patients with IR-PCa were retrospectively reviewed. APP4 was calculated based on biopsy reports. Multivariable competing risk analysis was then performed on optimized APP4 cutpoints to predict for biochemical failure (BF), androgen deprivation use for BF (ADT-BF) and development of metastases (MD). RESULTS: Median follow-up for the cohort was 5.2 (Inter Quartile Range: 2.9-6.6) years. Median baseline PSA was 7.3 (5.3-9.8) ng/mL. 234 (56.9%) patients had T1 and 177 (43.1%) had T2 disease. Median APP4 was 2.00 (0.75-7.50)%. 38 (9.3%) patients experienced BF. The optimal cutpoint of APP4 for BF was >3.3% with an area under the curve (AUC) of 0.66. 17 (4.1%) received ADT-BF. The ADT-BF cutpoint was >6.6% with an AUC of 0.72. Eight (2.0%) developed MD. The MD cutpoint was >17.5% with an AUC of 0.86. Using APP4 >3.3 vs ≤ 3.3, log-transformed baseline PSA ln(PSA) (HR 2.5, 1.1-6.1; p = 0.037) and APP4 (HR 2.3, 1.1-4.7; p = 0.031) predicted for BF. Using APP4 >6.6 vs ≤ 6.6, ln(PSA) (HR 4.2, 1.4-12.4; p = 0.010) and APP4 (HR 3.7, 1.4-10.0; p = 0.009) were predictive of ADT-BF. APP4 >17.5 vs ≤ 17.5 alone was predictive of MD (HR 25.7, 4.9-135.3; p < 0.001). CONCLUSION: APP4 cutpoints of >3.3%, >6.6% and >17.5% were strongly associated with increased risk of BF, ADT-BF and developing MD respectively. These findings may inform future practice when treating IR-PCa but require external validation.


Subject(s)
Brachytherapy/methods , Prostatic Neoplasms/radiotherapy , Aged , Biopsy , Humans , Male , Middle Aged , Neoplasm Grading , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Radiotherapy Dosage , Retrospective Studies
13.
Curr Oncol ; 25(2): 170-175, 2018 04.
Article in English | MEDLINE | ID: mdl-29719433

ABSTRACT

Three groups of men are at high risk of developing prostate cancer: men with a strong family history of prostate cancer, men of West African or Caribbean ancestry, and men with a germline pathogenic variant in a prostate cancer-associated gene. Despite the fact that those men constitute a significant portion of the male population in North America, few recommendations for prostate cancer screening specific to them have been developed. For men at general population risk for prostate cancer, screening based on prostate-specific antigen (psa) has remained controversial despite the abundance of literature on the topic. As a result, recommendations made by major screening authorities are inconsistent (ranging from no psa screening to baseline psa screening at age 45), allowing physicians to pick and choose how to screen their patients. The Male Oncology Research and Education (more) program is an observational research program that serves as an academic platform for multiple research foci. For its participants, serum and dna are biobanked, medical information is collected, and contact for relevant research-related opportunities is maintained. This research program is paired with a specialized clinic called the more clinic, where men at high risk are regularly screened for prostate cancer in a standard approach that includes physical examination and serum psa measurement. In this article, we describe the goals, participant accrual to date, and projects specific to this unique program.


Subject(s)
Biomedical Research/organization & administration , Early Detection of Cancer/methods , Prostatic Neoplasms/diagnosis , Ambulatory Care Facilities/organization & administration , Biological Specimen Banks/organization & administration , Genetic Predisposition to Disease , Humans , Kallikreins/blood , Male , Observational Studies as Topic , Ontario , Program Evaluation , Prostate-Specific Antigen/blood , Prostatic Neoplasms/etiology , Prostatic Neoplasms/genetics , Risk Factors
14.
Clin Oncol (R Coll Radiol) ; 30(6): 354-365, 2018 06.
Article in English | MEDLINE | ID: mdl-29496323

ABSTRACT

AIMS: Male breast cancer is a rare disease with limited evidence-based guidelines for treatment. This study aimed to identify demographic, pathological and clinical factors associated with its prognosis. MATERIALS AND METHODS: A retrospective review of 161 male breast cancer patients diagnosed at a single institution from 1987 to June 2017 was conducted. Patient demographics, disease characteristics, treatment and outcome were extracted and included in competing-risk analysis and the univariate Cox proportional hazard model for univariate analysis. Factors with P < 0.10 were included in multivariable analysis. RESULTS: The mean age at diagnosis was 67 years (standard deviation = 11.2) and the median follow-up duration was 5.3 years (range 0-25 years). There were 48 deaths, including 23 cancer-specific deaths. The actuarial median survival was 19.9 years. In multivariable analysis, factors associated with overall survival were size of tumours (hazard ratio 2.0; 95% confidence interval 1.4-2.7, P < 0.0001) and diagnosis of metastatic disease (hazard ratio 8.7; 95% confidence interval 1.9-40.6; P = 0.006). Of 138 patients without metastases at diagnoses, 11 had local-regional recurrence and 26 had distant metastases. In the multivariable model for local-regional recurrence, a more recent year of diagnosis was associated with reduced risk (hazard ratio 0.9, 95% confidence interval 0.8-1.0, P = 0.008), whereas more positive lymph nodes was associated with higher risk (hazard ratio 2.2, 95% confidence interval 1.2-4.0, P = 0.01). A higher risk of metastases was associated with more positive lymph nodes (hazard ratio 1.9; 95% confidence interval 1.1-3.3; P = 0.03) and tumour size (hazard ratio 1.8; 95% confidence interval 1.1-2.9; P = 0.01). A higher risk of any recurrence or metastases was associated with the number of positive nodes (hazard ratio 1.9; 95% confidence interval 1.2-3.0; P = 0.005) and tumour size (hazard ratio 1.6; 95% confidence interval 1.1-2.2; P = 0.01). CONCLUSION: In general, tumour size and more positive lymph nodes were associated with worse prognosis. Larger powered studies are needed to identify prognostic factors with smaller effect sizes.


Subject(s)
Breast Neoplasms, Male/therapy , Adult , Aged , Aged, 80 and over , Breast Neoplasms, Male/pathology , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Treatment Outcome
15.
Clin Oncol (R Coll Radiol) ; 29(11): 718-731, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28916284

ABSTRACT

AIMS: To conduct a cost-utility analysis comparing stereotactic body radiotherapy (SBRT) with low dose rate brachytherapy (LDR-BT) for localised prostate cancer (PCa). MATERIALS AND METHODS: A decision-analytic Markov model was developed from the healthcare payer perspective to simulate the history of a 66-year-old man with low-risk PCa. The model followed patients yearly over their remaining lifetimes. Health states included 'recurrence-free', 'biochemical recurrence' (BR), 'metastatic' and 'death'. Transition probabilities were based on a retrospective cohort analysis undertaken at our institution. Utilities were derived from the literature. Costs were assigned in 2015 Canadian dollars ($) and reflected Ontario's health system and departmental costs. Outcomes included quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratios. A willingness-to-pay threshold of $50 000/QALY was used. RESULTS: SBRT was the dominant strategy with 0.008LYs and 0.029QALYs gained and a reduction in cost of $2615. Under base case conditions, our results were sensitive to the BR probability associated with both strategies. LDR-BT becomes the preferred strategy if the BR with SBRT is 1.3*[baseline BR_SBRT] or if the BR with LDR-BT is 0.76*[baseline BR_LDR-BT]. When assuming the same BR for both strategies, LDR-BT becomes marginally more effective with 0.009QALYs gained at a cost of $272 848/QALY. CONCLUSIONS: SBRT represents an economically attractive radiation strategy. Further research should be carried out to provide longer-term follow-up and high-quality evidence.


Subject(s)
Brachytherapy/methods , Cost-Benefit Analysis/methods , Prostatic Neoplasms/economics , Radiosurgery/methods , Aged , Humans , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/therapy , Quality-Adjusted Life Years , Retrospective Studies
16.
Radiother Oncol ; 119(3): 371-80, 2016 06.
Article in English | MEDLINE | ID: mdl-27162159

ABSTRACT

Dose escalated radiotherapy improves outcomes for men with prostate cancer. A plateau for benefit from dose escalation using EBRT may not have been reached for some patients with higher risk disease. The use of increasingly conformal techniques, such as step and shoot IMRT or more recently VMAT, has allowed treatment intensification to be achieved whilst minimising associated increases in toxicity to surrounding normal structures. To support further safe dose escalation, the uncertainties in the treatment target position will need be minimised using optimal planning and image-guided radiotherapy (IGRT). In particular the increasing usage of profoundly hypo-fractionated stereotactic therapy is predicated on the ability to confidently direct treatment precisely to the intended target for the duration of each treatment. This article reviews published studies on the influences of varies types of motion on daily prostate position and how these may be mitigated to improve IGRT in future. In particular the role that MRI has played in the generation of data is discussed and the potential role of the MR-Linac in next-generation IGRT is discussed.


Subject(s)
Magnetic Resonance Imaging/methods , Prostatic Neoplasms/radiotherapy , Radiotherapy, Image-Guided/methods , Humans , Male , Motion , Radiotherapy, Intensity-Modulated/methods
17.
Br J Cancer ; 112(5): 777-82, 2015 Mar 03.
Article in English | MEDLINE | ID: mdl-25611301

ABSTRACT

At least half of all cancer patients will receive radiation therapy. Tumour radioresistance, or the failure to control certain tumours with this treatment, can result in locoregional recurrence; thus there is great interest in understanding the underlying biology and developing strategies to overcome this problem. The expanding investigation of microRNA in cancer suggests that these regulatory factors can influence the DNA damage response, the microenvironment and survival pathways, among other processes, and thereby may affect tumour radioresistance. As microRNA are readily detectable in tumours and biofluids, they hold promise as predictive biomarkers for therapy response and prognosis. This review highlights the current insights on the major ways that microRNA may contribute to tumour radiation response and whether their levels reflect treatment success. We conclude by applying the potential framework of future roles of miR in personalised radiotherapy using prostate cancer clinical management as an example.


Subject(s)
MicroRNAs/genetics , Neoplasms/genetics , Neoplasms/radiotherapy , Radiation Tolerance , DNA Damage , DNA Repair , Humans , MicroRNAs/metabolism , Precision Medicine , Tumor Microenvironment
18.
Clin Oncol (R Coll Radiol) ; 24(3): 183-9, 2012 Apr.
Article in English | MEDLINE | ID: mdl-21958729

ABSTRACT

AIMS: Determination of the risk of recurrence after local excision of ductal carcinoma in situ (DCIS) remains a challenge. Molecular profiling based on immunohistochemical staining to oestrogen receptor (ER), progesterone receptor (PR) and HER2neu improved risk prediction in invasive breast cancer, but few studies have evaluated if molecular classification of DCIS predicts local recurrence. We evaluated the expression of ER, PR and HER2neu in DCIS to determine if molecular classification predicts local recurrence after breast-conserving therapy for DCIS. MATERIALS AND METHODS: We reviewed the records of patients with DCIS treated between 1987 and 2000, carried out a pathology review and immunohistochemical staining for ER, PR and HER2neu and categorised cases into four molecular phenotypes [luminal A (ER+ and/or PR+, HER2neu-), luminal B (ER+ and/or PR+, HER2neu+), HER2neu subtype (ER-, PR-, HER2neu+), triple negative (ER-, PR-, HER2neu-)]. We evaluated the association between the molecular subtype and the development of local recurrence. RESULTS: In total, 180 cases of DCIS were included in the study (luminal A, n=113; luminal B, n=25; HER2neu type, n=29; triple negative, n=13). The median follow-up time was 8.7 years. We observed higher rates of local recurrence among luminal B (40%) and HER2neu type (38%) DCIS compared with luminal A (21%) and triple negative (15%) DCIS. On multivariable analysis, HER2neu overexpression was associated with an increased risk of local recurrence (hazard ratio=1.98; 95% confidence interval: 1.11, 3.53, P=0.02). CONCLUSION: HER2neu expression in DCIS is a significant predictor of local recurrence, whereas luminal A and triple negative phenotypes are associated with relatively low risks of local recurrence.


Subject(s)
Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/metabolism , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/surgery , Carcinoma, Intraductal, Noninfiltrating/metabolism , Carcinoma, Intraductal, Noninfiltrating/pathology , Carcinoma, Intraductal, Noninfiltrating/surgery , Female , Humans , Mastectomy, Segmental , Middle Aged , Neoplasm Invasiveness , Neoplasm Recurrence, Local/mortality , Neoplasm Staging , Prognosis , Survival Rate
19.
Clin Oncol (R Coll Radiol) ; 23(5): 333-8, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21084179

ABSTRACT

AIM: To estimate the growth rate of lymph nodes in patients on surveillance for testicular cancer who developed recurrent disease. MATERIALS AND METHODS: During a 7-year period, 318 patients at our institution were managed by surveillance and 39 relapsed (12.3%). The computed tomography scans of 28 patients (median age 32 years; range 19-51 years) who met our inclusion criteria and who developed recurrent disease in the abdomen/pelvis were retrospectively reviewed. Thirteen patients had non-seminoma and 15 had seminoma. To estimate the lymph node growth rate, the slope of lymph node size over time was calculated. RESULTS: The median length of time from orchiectomy to the recurrence computed tomography was 131 days (range 49-520) or about 4.4 months for non-seminoma patients and 373 days (range 129-675) or about 12.3 months for seminoma patients. The median size of the involved lymph node at final computed tomography for seminoma patients was 12 mm (range 9-31 mm) and for non-seminoma patients was 15 mm (range 10-56 mm). The median lymph node growth rate for patients with seminoma was 1.35 mm/month (range 0.62-4.56) and for patients with non-seminoma 2.99 mm/month (range 0.77-7.06); the difference in growth rates was statistically significant (P=0.029). CONCLUSIONS: There is a statistically significant faster growth rate of lymph nodes in patients with recurrent non-seminoma compared with patients with seminoma. This finding supports a more frequent computed tomography schedule during the first 2 years of surveillance in non-seminoma patients compared with seminoma patients.


Subject(s)
Lymph Nodes/diagnostic imaging , Neoplasms, Germ Cell and Embryonal/diagnostic imaging , Testicular Neoplasms/diagnostic imaging , Tomography, X-Ray Computed , Adult , Humans , Lymph Nodes/surgery , Male , Middle Aged , Neoplasms, Germ Cell and Embryonal/surgery , Orchiectomy , Seminoma/diagnostic imaging , Testicular Neoplasms/surgery
20.
Clin Oncol (R Coll Radiol) ; 20(8): 631-8, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18755578

ABSTRACT

AIM: To evaluate the effect of the addition of fused positron emission tomography-computed tomography (PET-CT) imaging vs computed tomography alone in the identification of the gross tumour volume (GTV) in patients with gastro-oesophageal carcinoma. MATERIALS AND METHODS: Ten patients with gastro-oesophageal cancer referred for radiation therapy underwent both (18F)fluoro-2-deoxy-d-glucose-PET (FDG-PET) and computed tomography in the treatment position. Image sets were anonymised and co-registered. Six radiation oncologists independently defined the GTV, first using the computed tomography data alone supplemented by standardised clinical and diagnostic imaging information, and second, using co-registered computed tomography and FDG-PET data (PET-CT). The standard deviation for both GTV length and volume (excluding involved lymph nodes) was taken as a measurement of inter-observer and intra-observer variability. Computer software that calculates volume overlap between contours was also used to generate an observer agreement index to compare intra- and inter-observer variability. RESULTS: The addition of FDG-PET imaging decreased the median standard deviation for tumour length from 10 mm (range 8.1-33.3, mean 12.4 mm) for computed tomography alone to 8mm (range 4.4-18.1, mean 8.1 mm) for PET-CT (P = 0.02). Eight of the 10 patients showed an increase in volume of overlap between observers with the addition of FDG-PET imaging to the contouring process (P = 0.05). The average observer agreement index in PET-CT was 72.7% compared with 69.1% when using computed tomography alone. There was significantly less intra-observer variability in all measures when PET-CT was used. The median standard deviation in length improved from 5.3 to 1.8 mm, the median standard deviation in volume improved from 4.5 to 3 cm3 and the median observer agreement index improved from 76.2 to 78.7% when computed tomography alone was compared with PET-CT. The corresponding P values were 0.001, 0.033 and 0.022, respectively. CONCLUSIONS: The addition of FDG-PET to computed tomography-based planning for the identification of primary tumour GTV in patients with gastro-oesophageal carcinoma decreases both inter-observer and intra-observer variability.


Subject(s)
Esophageal Neoplasms/diagnosis , Fluorodeoxyglucose F18 , Observer Variation , Positron-Emission Tomography/methods , Stomach Neoplasms/diagnosis , Tomography, X-Ray Computed , Esophageal Neoplasms/diagnostic imaging , Female , Humans , Male , Stomach Neoplasms/diagnostic imaging , Tomography, X-Ray Computed/methods
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